Exploring the common targets of well-differentiated and dedifferentiated retroperitoneal liposarcoma via gene co-expression analysis.

Objective: This study aimed to identify common therapeutic targets for well-differentiated and dedifferentiated retroperitoneal liposarcoma. Methods: Patient clinical data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, and survival differences were analyzed using the log-rank test. Gene expression data were sourced from the Gene Expression Omnibus (GEO) dataset GSE159659, with differential gene expression analysis conducted through GEO2R. Protein-protein interaction networks were developed using STRING and Cytoscape to identify key hub genes. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed using R, and transcription factors associated with the hub genes were predicted with TRRUST. Results: Significant survival differences were found between patients with well-differentiated and dedifferentiated retroperitoneal liposarcoma. Ninety-six differentially expressed genes with similar expression patterns were identified in both types. A protein-protein interaction network highlighted 12 hub genes and 24 transcription factors. Enrichment analysis pointed to the importance of lipid localization, storage, cytokine signaling, and metal ion absorption in both liposarcoma subtypes. Four potential therapeutic drugs were successfully predicted. Conclusion: This study identifies common molecular targets in well-differentiated and dedifferentiated retroperitoneal liposarcoma, providing new avenues for mechanistic studies and potential therapeutic development.

An Intragranular Segregation Structure Enables an Excellent Energy Storage Performance in Composite Dielectrics through Delayed Saturation Polarization.

An electrostatic capacitor for energy storage is an important basic component of pulse power electronics. The electrical breakdown strength (Eb) of normal ferroelectrics is low, which limits their application in dielectric energy storage. Constructing a 0-3-type composite dielectric, that is, introducing an insulating metallic oxide into the ferroelectric matrix, can greatly enhance Eb. Unfortunately, an intergranular secondary phase typically forms that causes large attenuation of the dielectric constant, which leads to limited improvement of energy storage performance. In this work, a composite ceramic with an intragranular segregation structure was intentionally designed using the BaTiO3-BaZrO3-CaTiO3 (BCZT) system as an example. Compared with those of a BCZT solid solution without a secondary phase and a BCZT composite with a grain-boundary secondary phase, the rationally designed BCZT composite with an intragranular secondary phase delivered a large recoverable energy density of 5.86 J/cm3 and high efficiency of 86.7% at a moderate electric field of 550 kV/cm. Such performance was achieved because the intragranular segregation structure displayed delayed saturation polarization with a high Eb. This microstructural engineering strategy is generally applicable to optimize composite dielectrics to meet the demands of high-performance energy storage capacitors.

Effectiveness and impact factors of passive convergence-permeable reactive barrier (PC-PRB): Insights from tracer simulation study.

Passive convergence-permeable reactive barrier (PC-PRB) represents a green and sustainable technology for in-situ remediation of contaminated groundwater. A laboratory-scale PC-PRB tracer simulation system was established to quantify its contaminant plume capture performance using image analysis method. Results indicate that PC-PRB captures the plume 65% wider than C-PRB, which means that fewer PRB sizes and materials volume would be necessary to treat an equivalent contaminated plume. This improvement is due to a significant drawdown within the PC-PRB's passive well, known as the passive hydraulic decompression-convergent flow effect. We further evaluated the effects of water pipe length, hydraulic gradient, and media particle size on PC-PRB's plume capture performance. Results indicate that an increased water pipe length enhances the PC-PRB's plume capture capacity due to greater well drawdown. PC-PRB not only captures the plume but also acts as a hydraulic barrier. The retardation effect of PC-PRB on plume migration increases with water pipe length. Conversely, both hydraulic gradient and media particle size impact the plume capture capacity of PC-PRB by modifying groundwater flow velocity and pollutant dispersion. An increase in either hydraulic gradient or media particle size decreases the plume capture performance of PC-PRB. Therefore, PC-PRB technology may be more effective in contaminated sites characterized by low hydraulic gradients and permeability. Overall, PC-PRB demonstrates significant effectiveness in enhancing plume capture performance, which can notably reduce remediation costs and environmental footprint, broadening its application scope.

Pseudomonas chlororaphis subsp. aurantiaca Stimulates Lateral Root Development by Integrating Auxin and Reactive Oxygen Species Signaling in Arabidopsis.

Plant growth-promoting rhizobacteria (PGPR) can promote lateral root formation, while the underlying mechanisms are not fully understood. Here, we found that Pseudomonas chlororaphis subsp. aurantiaca inoculation enhanced auxin accumulation in lateral root primordia (LRP). Upon reaching LRPs, auxin activated the AUXIN RESPONSE FACTOR 7 and 19 (ARF7/19) and promoted lateral root formation in Arabidopsis. Moreover, we found that reactive oxygen species (ROS) is required for auxin-dependent lateral root emergence, and P. chlororaphis upregulated the expression of RESPIRATORY BURST OXIDASE D and F (RBOHD/F), leading to the accumulation of ROS in LRP. Although scavenging ROS or rbohd/f mutants exhibited decreased lateral roots after P. chlororaphis inoculation, the bacteria-triggered auxin signals were not altered. Conversely, the application of auxin or mutants defective in auxin signaling disturbed P. chlororaphis-derived ROS accumulation in lateral roots. Collectively, these results suggest that ARF7/19-dependent auxin signaling activates RBOHD/F to produce ROS, coordinately facilitating lateral root development after P. chlororaphis treatment.

Prion-like Proteins in Plants: Key Regulators of Development and Environmental Adaptation via Phase Separation.

Prion-like domains (PrLDs), a unique type of low-complexity domain (LCD) or intrinsically disordered region (IDR), have been shown to mediate protein liquid-liquid phase separation (LLPS). Recent research has increasingly focused on how prion-like proteins (PrLPs) regulate plant growth, development, and stress responses. This review provides a comprehensive overview of plant PrLPs. We analyze the structural features of PrLPs and the mechanisms by which PrLPs undergo LLPS. Through gene ontology (GO) analysis, we highlight the diverse molecular functions of PrLPs and explore how PrLPs influence plant development and stress responses via phase separation. Finally, we address unresolved questions about PrLP regulatory mechanisms, offering prospects for future research.

A Competition for the Diagnosis of Myopic Maculopathy by Artificial Intelligence Algorithms.

Importance: Myopic maculopathy (MM) is a major cause of vision impairment globally. Artificial intelligence (AI) and deep learning (DL) algorithms for detecting MM from fundus images could potentially improve diagnosis and assist screening in a variety of health care settings. Objectives: To evaluate DL algorithms for MM classification and segmentation and compare their performance with that of ophthalmologists. Design, Setting, and Participants: The Myopic Maculopathy Analysis Challenge (MMAC) was an international competition to develop automated solutions for 3 tasks: (1) MM classification, (2) segmentation of MM plus lesions, and (3) spherical equivalent (SE) prediction. Participants were provided 3 subdatasets containing 2306, 294, and 2003 fundus images, respectively, with which to build algorithms. A group of 5 ophthalmologists evaluated the same test sets for tasks 1 and 2 to ascertain performance. Results from model ensembles, which combined outcomes from multiple algorithms submitted by MMAC participants, were compared with each individual submitted algorithm. This study was conducted from March 1, 2023, to March 30, 2024, and data were analyzed from January 15, 2024, to March 30, 2024. Exposure: DL algorithms submitted as part of the MMAC competition or ophthalmologist interpretation. Main Outcomes and Measures: MM classification was evaluated by quadratic-weighted κ (QWK), F1 score, sensitivity, and specificity. MM plus lesions segmentation was evaluated by dice similarity coefficient (DSC), and SE prediction was evaluated by R2 and mean absolute error (MAE). Results: The 3 tasks were completed by 7, 4, and 4 teams, respectively. MM classification algorithms achieved a QWK range of 0.866 to 0.901, an F1 score range of 0.675 to 0.781, a sensitivity range of 0.667 to 0.778, and a specificity range of 0.931 to 0.945. MM plus lesions segmentation algorithms achieved a DSC range of 0.664 to 0.687 for lacquer cracks (LC), 0.579 to 0.673 for choroidal neovascularization, and 0.768 to 0.841 for Fuchs spot (FS). SE prediction algorithms achieved an R2 range of 0.791 to 0.874 and an MAE range of 0.708 to 0.943. Model ensemble results achieved the best performance compared to each submitted algorithms, and the model ensemble outperformed ophthalmologists at MM classification in sensitivity (0.801; 95% CI, 0.764-0.840 vs 0.727; 95% CI, 0.684-0.768; P = .006) and specificity (0.946; 95% CI, 0.939-0.954 vs 0.933; 95% CI, 0.925-0.941; P = .009), LC segmentation (DSC, 0.698; 95% CI, 0.649-0.745 vs DSC, 0.570; 95% CI, 0.515-0.625; P < .001), and FS segmentation (DSC, 0.863; 95% CI, 0.831-0.888 vs DSC, 0.790; 95% CI, 0.742-0.830; P < .001). Conclusions and Relevance: In this diagnostic study, 15 AI models for MM classification and segmentation on a public dataset made available for the MMAC competition were validated and evaluated, with some models achieving better diagnostic performance than ophthalmologists.

APIS: a paired CT-MRI dataset for ischemic stroke segmentation - methods and challenges.

Stroke, the second leading cause of mortality globally, predominantly results from ischemic conditions. Immediate attention and diagnosis, related to the characterization of brain lesions, play a crucial role in patient prognosis. Standard stroke protocols include an initial evaluation from a non-contrast CT to discriminate between hemorrhage and ischemia. However, non-contrast CTs lack sensitivity in detecting subtle ischemic changes in this phase. Alternatively, diffusion-weighted MRI studies provide enhanced capabilities, yet are constrained by limited availability and higher costs. Hence, we idealize new approaches that integrate ADC stroke lesion findings into CT, to enhance the analysis and accelerate stroke patient management. This study details a public challenge where scientists applied top computational strategies to delineate stroke lesions on CT scans, utilizing paired ADC information. Also, it constitutes the first effort to build a paired dataset with NCCT and ADC studies of acute ischemic stroke patients. Submitted algorithms were validated with respect to the references of two expert radiologists. The best achieved Dice score was 0.2 over a test study with 36 patient studies. Despite all the teams employing specialized deep learning tools, results reveal limitations of computational approaches to support the segmentation of small lesions with heterogeneous density.

Race/ethnicity and socioeconomic status affect the assessment of lipoprotein(a) levels in clinical practice.

BACKGROUND AND OBJECTIVE: High Lp(a) levels are a risk factor for ASCVD, however Lp(a) ordering in clinical practice is low. This study examines how race/ethnicity and socioeconomic status influence Lp(a) ordering. METHODS: This is a single center, retrospective study (2/1/2020-6/30/2023) using electronic medical records of adults with at least one personal ICD-10 diagnosis of ASCVD, aortic valve stenosis, resistant hypercholesterolemia (LDL-C >160 mg/dL on statin therapy), and family history of ASCVD or high Lp(a). We evaluated Lp(a) level differences among racial/ethnic groups and sexes. We also assessed associations between diagnosis type, diagnosis number, age at diagnosis, race/ethnicity, socioeconomic score (based on zip codes), public health coverage and the presence of Lp(a) orders. RESULTS: 4 % of our cohort (N=2,249 in 56,833) had an Lp(a) order (17.3 % of whom identified as Hispanic, 8.7 % non-Hispanic Black, 47.5 % non-Hispanic White, and 27 % Asian/other). Non-Hispanic Black and Hispanic patients had lower rates of Lp(a) orders (0.17 % and 0.28 %, respectively) when compared to non-Hispanic White patients (2.35 %), p < 0.001, however, their median Lp(a) levels were higher, p < 0.001. Individuals on Medicaid or belonging to deprived socioeconomic groups were less likely to have an Lp(a) order (IRR = 0.40, p < 0.001 and IRR = 0.39, p < 0.001 respectively). Certain diagnosis (carotid stenosis, family history of ASCVD and FH) and multiple diagnoses (>2) resulted in more Lp(a) orders compared to only one diagnosis (p < 0.001). CONCLUSIONS: Lp(a) ordering is low in patients with or at risk for ASCVD. Non-Hispanic Black and Hispanic patients are less likely to have an Lp(a) order. Individuals on Medicaid and residing in socioeconomically deprived neighborhoods are less like have an Lp(a) order. Lp(a) orders depend on the type and number of patients' diagnoses.

Chemiluminescence detection of kanamycin by DNA aptamer regulating peroxidase-like activity of Co3O4 nanoparticles.

Kanamycin (KAN) is widely used as a growth hormone analog and an antibacterial agent. However, abuse of this substance has resulted in the accumulation of excessive residue levels in foods of animal origin, which presents a significant risk to human health. A chemiluminescent aptasensor was constructed for the rapid quantitative detection of KAN by combining the properties of Co3O4 nanoparticles (Co3O4 NPs) nanozyme activity and DNA aptamer with high specificity. The DNA aptamer/Co3O4 NPs nanozyme regulated the chemiluminescence signal by exploiting the chemiluminescent properties of luminol oxidation by H2O2. Specific binding of KAN to the aptamer led to the formation of a steric hindrance block in the solution, which inhibited the activity of nanozyme and reduced signal intensity. The degree of signal reduction is related to the concentration of KAN. Under optimal conditions, there was good linearity between KAN concentration and chemiluminescence signal intensity in the range of 0.5-8.0 µΜ, with a detection limit of 0.26 µΜ. The detection system performed well in the presence of competing antibiotics and was virtually unaffected. The method was also suitable for the detection of KAN in milk samples with sample recoveries of 97.8%-99.1%. The chemiluminescence sensor has the advantages of low cost, specificity, and sensitivity, and does not require an external light source or modification of the nucleic acid aptamer which makes it a promising candidate for applications in the field of food detection.

c-Jun N-terminal kinase signaling in aging.

Aging encompasses a wide array of detrimental effects that compromise physiological functions, elevate the risk of chronic diseases, and impair cognitive abilities. However, the precise underlying mechanisms, particularly the involvement of specific molecular regulatory proteins in the aging process, remain insufficiently understood. Emerging evidence indicates that c-Jun N-terminal kinase (JNK) serves as a potential regulator within the intricate molecular clock governing aging-related processes. JNK demonstrates the ability to diminish telomerase reverse transcriptase activity, elevate ß-galactosidase activity, and induce telomere shortening, thereby contributing to immune system aging. Moreover, the circadian rhythm protein is implicated in JNK-mediated aging. Through this comprehensive review, we meticulously elucidate the intricate regulatory mechanisms orchestrated by JNK signaling in aging processes, offering unprecedented molecular insights with significant implications and highlighting potential therapeutic targets. We also explore the translational impact of targeting JNK signaling for interventions aimed at extending healthspan and promoting longevity.

A Modular Three-Component Approach for Site-selective Tandem Arene Thiophosphorylation.

Thiophosphates serve as pivotal reagents within the realms of both organic and inorganic synthesis, with their most notable applications observed in agricultural chemistry. This manuscript delineates a modular three-component synthetic strategy for site-selective arene C-H thiophosphorylation with thianthrenium salt, 1,4-diazabicyclo[2.2.2]octane-sulfur dioxide (DABSO), and diarylphosphine oxides as substrates. This approach facilitates the metal-free and green synthesis of a diverse spectrum of S-aryl phosphorothioates through C-H functionalization and late-stage modification showcasing practicality and broad applicability.

Small apolipoprotein(a) isoforms may predict primary patency following peripheral arterial revascularization.

Background: High lipoprotein (a) [Lp(a)] is associated with adverse limb events in patients undergoing lower extremity revascularization. Lp(a) levels are genetically pre-determined, with LPA gene encoding for two apolipoprotein (a) [apo(a)] isoforms. Isoform size variations are driven by the number of kringle IV type 2 (KIV-2) repeats. Lp(a) levels are inversely correlated with isoform size. In this study, we examined the role of Lp(a) levels, apo(a) size, and inflammatory markers with lower extremity revascularization outcomes. Methods: Twenty-five subjects with chronic peripheral arterial disease (PAD) underwent open or endovascular lower extremity revascularization (mean age, 66.7 ± 9.7 years; Female = 12; Male = 13; Black = 8; Hispanic = 5; and White = 12). Pre- and postoperative medical history, self-reported symptoms, ankle-brachial indices (ABIs), and lower extremity duplex ultrasounds were obtained. Plasma Lp(a), apoB100, lipid panel, and pro-inflammatory markers (IL-6, IL-18, hs-CRP, TNFα) were assayed preoperatively. Isoform size was estimated using gel electrophoresis and weighted isoform size (wIS) calculated based on % isoform expression. Firth logistic regression was used to examine the relationship between Lp(a) levels and wIS with procedural outcomes: symptoms (better/worse), early primary patency at 2 to 4 weeks, ABIs, and reintervention within 3 to 6 months. We controlled for age, sex, history of diabetes, smoking, statin, antiplatelet, and anticoagulation use. Results: Median plasma Lp(a) level was 108 (interrquartile range, 44-301) nmol/L. The mean apoB100 level was 168.0 ± 65.8 mg/dL. These values were not statistically different among races. We found no association between Lp(a) levels and wIS with measured plasma pro-inflammatory markers. However, smaller apo(a) wIS was associated with occlusion of the treated lesion(s) in the postoperative period (odds ratio, 1.97; 95% confidence interval, 1.01-3.86; P < .05). The relationship of smaller apo(a) wIS with reintervention was not as strong (odds ratio, 1.57; 95% confidence interval, 0.96-2.56; P = .07). We observed no association between wIS with patient reported symptoms or change in ABIs. Conclusions: In this small study, subjects with smaller apo(a) isoform size undergoing peripheral arterial revascularization were more likely to experience occlusion in the postoperative period and/or require reintervention. Larger cohort studies identifying the mechanism and validating these preliminary data are needed to improve understanding of long-term peripheral vascular outcomes.

CRISPR screens reveal convergent targeting strategies against evolutionarily distinct chemoresistance in cancer.

Resistance to chemotherapy has been a major hurdle that limits therapeutic benefits for many types of cancer. Here we systematically identify genetic drivers underlying chemoresistance by performing 30 genome-scale CRISPR knockout screens for seven chemotherapeutic agents in multiple cancer cells. Chemoresistance genes vary between conditions primarily due to distinct genetic background and mechanism of action of drugs, manifesting heterogeneous and multiplexed routes towards chemoresistance. By focusing on oxaliplatin and irinotecan resistance in colorectal cancer, we unravel that evolutionarily distinct chemoresistance can share consensus vulnerabilities identified by 26 second-round CRISPR screens with druggable gene library. We further pinpoint PLK4 as a therapeutic target to overcome oxaliplatin resistance in various models via genetic ablation or pharmacological inhibition, highlighting a single-agent strategy to antagonize evolutionarily distinct chemoresistance. Our study not only provides resources and insights into the molecular basis of chemoresistance, but also proposes potential biomarkers and therapeutic strategies against such resistance.

Relationship and mechanisms between internet use and physical exercise among middle- and younger-aged groups.

The "Internet Plus" era has established a closer connection between sports and individuals. This study used data from the 2018 China Family Panel Studies and focused on the middle- and younger-aged population aged 15 to 59 years. Employing a negative binomial regression model, this study empirically analyzed the impact of Internet use on physical exercise and its internal mechanisms among this population. The findings revealed that (1) Internet use significantly promoted physical exercise in the middle- and younger-aged population, with the frequency of physical exercise increasing to 1.549 times the original value; (2) The positive effects of the internet on physical exercise outweighed the negative effects, with online learning and entertainment enhancing physical exercise and online socialization limiting it. Specifically, online learning and entertainment increased the frequency of physical exercise among the middle- and younger-aged population by 0.063 and 0.018, respectively. Online socialization reduced the frequency by 0.023; and (3) The influence of internet use on physical exercise varies; significantly, it positively affects the exercise frequency among individuals over 35 years old and shows a positive correlation with employment status, including both employed individuals and those out of the labor market. The positive role of Internet use in encouraging physical exercise participation among the middle- and young-aged groups should be valued and enhanced.

Inverse design of mid-infrared diamond waveguide beam splitter.

Diamond is a supreme material for mid-infrared (MIR) integrated photonics as it has a transparency window up to 20 µm that covers the entire fingerprint region. However, its relatively low refractive index poses a challenge in designing an MIR diamond functional device with both small footprint and high transmission efficiency. Here we propose and demonstrate the inverse design of an MIR diamond waveguide beam splitter operating at the wavelength of 15 µm with a small footprint of ∼15 µm × âˆ¼15 µm and a total transmission efficiency above 95%. Our work paves a new avenue for the design of compact and high-efficiency MIR diamond photonic devices.

Design, synthesis, and biological evaluation of naphthalene imidazo[1,2-b]pyridazine hybrid derivatives as VEGFR selective inhibitors.

The vascular endothelial growth factor receptor (VEGFR) is a receptor tyrosine kinase that is regarded as an emerging target for abnormal angiogenesis diseases. In this study, novel naphthalene imidazo[1,2-b]pyridazine hybrids as VEGFR selective inhibitors were designed and synthesized using a scaffold hopping strategy based on ponatinib, a multitarget kinase inhibitor. Among the evaluated compounds, derivative 9k (WS-011) demonstrated the most potent inhibitory potency against VEGFR-2 (IC50 = 8.4 nM) and displayed superior VEGFR selectivity over a panel of 70 kinases compared with ponatinib. Furthermore, 9k possessed good cytotoxic effects on various cancer cell lines, especially the colon cancer HT-29 cells, with an acceptable oral bioavailability. Moreover, 9k significantly inhibited the migration and invasion of human umbilical vein endothelial cells (HUVEC) cells and induced apoptosis through the upregulation of apoptotic proteins in HT-29 cells. 9k also effectively suppressed the activation of VEGFR-2 signaling pathways, which in turn inhibited the growth of HT-29 cells and the tube formation of HUVECs in vitro. All of the findings revealed that 9k could be considered a promising antiangiogenesis lead that merits further investigation.

Tracing residual patterns and microbial communities of pharmaceuticals and personal care products from 17 urban landfills leachate in China.

Landfill leachate contributes significantly to the presence of pharmaceuticals and personal care products (PPCPs) in the environment, and is a crucial source of contamination. To examine the occurrence of PPCPs and microbial communities, this study comprehensively investigated the concentrations of PPCPs and the abundance of microorganisms in the leachate from 17 municipal landfills across China. Generally, Lidocaine, Linear alkylbenzene sulfonate-C11, and Triclocarban, which are closely associated with human activities, exhibited a detection frequency of 100 % in the leachate. Driven by consumer demand, analgesic and antipyretic drugs have emerged as the most prominent PPCPs in leachate (accounting for 39.9 %). Notably, the Ibuprofen peaked at 56.3 µg/L. Regarding spatial distribution, the contamination of PPCPs in leachates from the eastern regions of China was significantly higher than that in other regions, owing to the level of economic development and demographic factors. Furthermore, the 16S rRNA results revealed significant differences in microbial communities among the leachates from different areas. Although the impact of PPCPs on microbial communities may not be as significant as that of environmental factors, most positive correlations between PPCPs and microorganisms indicate their potential role in providing nutrients and creating favorable conditions for microbial growth. Overall, this research offers new perspectives on the residual features of PPCPs and the microbial community structure in leachates from various regions in China.

Ancestry specific distribution of LPA Kringle IV-Type-2 genetic variants highlight associations to apo(a) copy number, glucose, and hypertension.

Background: High Lp(a) levels contribute to atherosclerotic cardiovascular disease and are tightly regulated by the LPA gene . Lp(a) levels have an inverse correlation with LPA Kringle IV Type-2 (KIV-2) copy number (CN). Black (B) and Hispanic (H) individuals exhibit higher levels of Lp(a), and rates of CVD compared to non-Hispanic Whites (NHW). Therefore, we investigated genetic variations in the LPA KIV-2 region across three ancestries and their associations with metabolic risk factors. Methods: Using published pipelines, we analyzed a multi-ethnic whole exome dataset comprising 3,817 participants from the Washington Heights and Inwood Columbia Aging Project (WHICAP): 886 [NHW (23%), 1,811 Caribbean (C) H (47%), and 1,120 B individuals (29%). Rare and common variants (alternative allele carrier frequency, CF < 0.01 or > 0.99 and 0.01 < CF < 0.99, respectively) were identified and KIV-2 CN estimated. The associations of variants and CN with history of heart disease, hypertension (HTN), stroke, lipid levels and clinical diagnosis of Alzheimer's disease (AD) was assessed. A small pilot provided in-silico validation of study findings. Results: We report 1421 variants in the LPA KIV-2 repeat region, comprising 267 exonic and 1154 intronic variants. 61.4% of the exonic variants have not been previously described. Three novel exonic variants significantly increase the risk of HTN across all ethnic groups: 4785-C/A (frequency = 78%, odds ratio [OR] = 1.45, p = 0.032), 727-T/C (frequency = 96%, OR = 2.11, p = 0.032), and 723-A/G (frequency = 96%, OR = 1.97, p = 0.038). Additionally, six intronic variants showed associations with HTN: 166-G/A, 387-G/C, 402-G/A, 4527-A/T, 4541-G/A, and 4653-A/T. One intronic variant, 412-C/T, was associated with decreased blood glucose levels (frequency = 72%, ß = -14.52, p = 0.02).Three of the associations were not affected after adjusting for LPA KIV-2 CN: 412-C/T (ß = -14.2, p = 0.03), 166-G/A (OR = 1.41, p = 0.05), and 387-G/C (OR = 1.40, p = 0.05). KIV CN itself was significantly associated with 314 variants and was negatively correlated with plasma total cholesterol levels. Conclusions: In three ancestry groups, we identify novel rare and common LPA KIV-2 region variants. We report new associations of variants with HTN and Glucose levels. These results underscore the genetic complexity of the LPA KIV-2 region in influencing cardiovascular and metabolic health, suggesting potential genetic regulation of pathways that can be studied for research and therapeutic interventions.

An electrochemical aptasensor for zearalenone detection based on the Co3O4/MoS2/Au nanocomposites and hybrid chain reaction.

An electrochemical aptasensor was used for the fast and sensitive detection of zearalenone (ZEN) based on the combination of Co3O4/MoS2/Au nanocomposites and the hybrid chain reaction (HCR). The glassy carbon electrode was coated with Co3O4/MoS2/Au nanomaterials to immobilize the ZEN-cDNA that had been bound with ZEN-Apt by the principle of base complementary pairing. In the absence of ZEN, the HCR could not be triggered because the ZEN-cDNA could not be exposed. After ZEN was added to the surface of the electrode, a complex structure was produced on the modified electrode by the combination of ZEN and ZEN-Apt. Therefore, the ZEN-cDNA can raise the HCR to produce the long-strand dsDNA structure. Due to the formation of dsDNA, the methylene blue (MB) could be inserted into the superstructure of branched DNA and the peak currents of the MB redox signal dramatically increased. So the concentration of ZEN could be detected by the change of signal intensity. Under optimized conditions, the developed electrochemical biosensing strategy showed an outstanding linear detection range of 1.0×10-10 mol/L to 1.0×10-6 mol/L, a low detection limit (LOD) of 8.5×10-11 mol/L with desirable selectivity and stability. Therefore, the fabricated platform possessed a great application potential in fields of food safety, medical detection, and drug analysis.

Repeatability of a Virtual Reality Headset Perimeter in Glaucoma and Ocular Hypertensive Patients.

Purpose: The VisuALL S is an automated, static threshold, virtual reality-based perimeter for mobile evaluation of the visual field. We examined same-day and 3-month repeatability. Methods: Adult participants with a diagnosis of glaucoma or ocular hypertension underwent two VisuALL 24-2 Normal T- Full threshold strategy tests at baseline and one additional exam at 3 months for each eligible eye. Spearman, intraclass correlation coefficients (ICCs), and Bland-Altman plots were used to assess the correlation of individual point sensitivities and mean deviation (MD) among three tests. Results: Eighty-eight eyes (44 participants) were included. Average age was 68.1 ± 14.3 years, and 60.7% were male. VisuALL MD was highly correlated between tests (intravisit: r = 0.89, intervisit: r = 0.82; P < 0.001 for both). Bland-Altman analysis showed an average difference in intravisit MD of -0.67 dB (95% confidence interval [CI], -6.04 to 4.71 dB) and -0.15 dB (95% CI, -8.04 to 7.73 dB) for intervisit exams. Eight-five percent of pointwise intravisit ICCs were above 0.75 (range, 0.63 to 0.93), and 65% of pointwise intervisit ICCs were above 0.75 (range, 0.55 to 0.91). Conclusions: VisuALL demonstrated high correlation of MD between tests and good repeatability for individual point sensitivities among three tests in 3 months, except at the points around the blind spot and superiorly. Translational Relevance: The preliminary reproducibility results for VisuALL are encouraging. Its portable design makes it a potentially useful tool for patients with glaucoma, enabling more frequent assessments both at home and in clinical settings.